The Clinical Core provides expertise in radiological, oncological, surgical, pathological and statistical methods in support of clinical study of the project-based imaging modalities. It serves all four Projects on an equal basis while also interacting with the Computational Core on critical data management and analysis of the alternative imaging exams. During the current funding period, the Core concept of centralized clinical responsibility, leadership and expertise has proved to (i) improve quality control and provide standardization of record keeping, alternative exam delivery, and data analysis (ii) enhance subject accruals through use of a focused recruitment strategy which increases enrollments and eliminates competition by prioritizing protocols and (iii) ensure an integrated dissemination and sharing of clinical experiences and image analysis amongst all Project components. In addition to these economies of effort and increased quality controls, the Clinical Core has provided a uniform framework for comparing and analyzing the respective imaging methods in common cohorts of women, which would otherwise be difficult, if not impossible, to achieve. During the proposed continuation period, the Core will coordinate and execute the clinical strategic plan to meet the overall Program objectives of estimating the effectiveness and determining the readiness of these breast imaging methods for multi-center trials formulated to evaluate their efficacy in differential diagnosis and for further study of their role in treatment prognosis and therapy monitoring. This includes (1) clinical access, resources, research expertise and statistical methodology to prepare the new imaging technologies for clinical application and evaluation, (2) evaluation of the potential of the four new imaging modalities for differential diagnosis and generation of pilot data on therapy monitoring and treatment prognosis by conducting additional clinical studies of screening abnormalities recommended for biopsy, palpable masses on clinical breast exams and serial imaging of locally-advanced cancers receiving neoadjuvant therapy prior to surgical resection and (3) establishing correlations between imaged properties in vivo and direct property measurements at time of surgery and pathological findings in order to validate the utility of the imaging techniques and improve understanding of the biological basis of image contrast. Upon completion of these aims, specific recommendations and plans will be developed for multi-center imaging studies of any or all of the alternative modalities either alone or in combination, including identification of potential partner institutions, trial designs, quality control and data management procedures, pathological endpoints and other protocol specifications.